A new study offers fresh evidence that popping a daily aspirin is associated with a lower risk of dying from cancer, but the size of the potential protective effect may be smaller than previous research has suggested.

In March, a provocative study by researchers at University of Oxford found that people who took an aspirin a day for five years saw a 37% reduced risk of cancer death, and those taking aspirin for up to 10 years saw a 15% lower risk, compared with non-aspirin users. That data came from a pooled analysis of randomized trials looking at the use of aspirin to ward off heart disease.

But the overall evidence on the issue was sketchy: two other large randomized trials of aspirin taken every other day found no effect on cancer death, while three large observational studies reported conflicting results. So researchers from the Epidemiology Research Program at the American Cancer Society in Atlanta took another look at the long-term effects of daily aspirin use on cancer death risk in a separate cohort of patients.

The new study attempted to replicate the findings of earlier pooled-analysis by following up with people who had taken aspirin daily for at least five years. The researchers, led by Eric Jacobs at the American Cancer Society, examined data on 100,139 predominantly white men and women over age 60 with no history of cancer, who participated in the Cancer Prevention Study II Nutrition Cohort. In 1992-93, when the participants were first enrolled, they completed questionnaires detailing their aspirin use; they did so again in 1997, and every two years thereafter until 2003. The researchers tracked cancer deaths in the participants until 2008.

Between 1997 and 2008, 5,138 people died of cancer. The researchers found that those taking a daily dose of aspirin for at least five years had a 16% lower risk of cancer death than people who didn’t take aspirin. The effect was similar regardless of how long people took aspirin — more or less than five years. The overall reduction in risk was driven by a 40% lower mortality risk from gastrointestinal tract cancers (cancers of the esophagus, stomach, small intestine, colon and rectum) and a smaller but significant reduction in risk of death from other cancers.

It’s a powerful finding, but the size of the effect the researchers uncovered was considerably smaller than the 37% reduction in cancer death risk found in the previous analysis. The authors note, however, that because their study was observational, and not randomized, it could have underestimated the association between aspirin and cancer death risk if daily aspirin takers also had underlying cancer risk factors that the study didn’t control for. It could have also overestimated the effect if aspirin takers were more likely to have other qualities that independently lowered the risk of cancer death, such as seeking immediate medical attention at the first signs of cancer.

Still, given the large size of the study, the findings are significant. “Even a relatively modest benefit with respect to overall cancer mortality could still meaningfully influence the balances of risks and benefits of prophylactic aspirin use,” the authors wrote.

In an accompanying editorial, Dr. John Baron of the department of medicine at the University of North Carolina School of Medicine wrote that the “big picture on aspirin use and cancer is very positive”:

The drug clearly reduces the incidence and mortality from luminal gastrointestinal cancers, and it may similarly affect other cancers. This is exciting: simply taking a pill can prevent cancer incidence and cancer death.

He added, however, “just because aspirin is effective does not mean it necessarily should be used.” For one thing, it’s not entirely clear how aspirin may work to stave off cancer. And the painkiller’s possible side effects, notably the risk of gastrointestinal bleeding, even from taking low-dose aspirin, should be be taken into account when deciding whether to use it:

Aspirin is a real drug, with definite toxicity. As for any preventative intervention, the benefits must be balanced against the risks, particularly when the benefits are delayed whereas the risks are not.

In other words, the protective effects of aspirin against cancer could take some 10 years to materialize, but meanwhile, patients may suffer side effects of bleeding during that period.

For now, the researchers say it is too soon to recommend that people start taking aspirin just for the prevention of cancer.

The study was published in the Journal of the National Cancer Institute.